The pathogenesis of most cases of heart failure is an important unsolved problem. We strongly feel that cardiac mitochondrial dysfunction and the resultant inability to synthesize ATP invariably results in cardiac failure. A control mechanism regulates the transition between two functional states of cardiac mitochondria - the aggregated and orthodox configurational states respectively. The capacity for ATP synthesis is operative in only one of the two states (aggregated configuration). Evidence is now available that reagents (Ca ions, antimycin, valinomycin) that induce the orthodox configuration also suppress cardiac function in a dog heart-lung preparation. Reliable experimental techniques have been developed for evaluating this correlation between the configurational changes measured electron microscopically in biopsied samples and cardiac power as determined by a critical set of measurements. A testing program is outlined for a rigorous evaluation of this altered mitochondria state - cardiac function correlation which covers both the induction and reversal of configurational changes as well as the reversal of other mitochondrial abnormalities. The crucial nature of this correlation for the diagnosis and treatment of cardiac dysfunction as well as the relevance of the proposed investigation to the problem of trauma and cardiac preservation is pointed out.